Apparatus for delivering ions to a mass analyzer. The apparatus includes a time of flight ion guide, a pulsing device for receiving a continuous ion stream containing ions of different atomic mass and for delivering pulses of ions to the ion guide wherein ions in each of the pulses of ions exit the ion guide in ascending order of their atomic mass, and a gating device at the exit end of the ion guide for allowing ions of a predetermined atomic mass to pass to the mass analyzer.
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25. A method of delivering ions from a continuous ion stream containing ions of different atomic mass analyzer, said method comprising:
(a) converting said continuous ion stream into pulses of ions;
(b) guiding each of said pulses of ions along a time of flight path toward said mass analyzer so that ions in each of said pulses of ions reach an end of said time of flight path in ascending order of their atomic mash; and
(c) employing a qating device comprising a first part and a second part, said first part having an aperture, wherein electrical potentials applied to said first part and said second part of said gating device selectively allow a portion of each of said pulses of ions to enter said mass analyzer from the end of said time of flight path and preventing the remainder of each of said pulses of ions from entering said mass analyzer.
20. A method of delivery ions from a continuous ion stream containing ions of different atomic mass to a mass analyzer, said method comprising:
(a) converting said continuous ion stream into pulses of ions;
(b) guiding each of said pulses of ions along a time of flight path toward said mass analyzer so that ions in each of said pulses of ions reach an end of said time of flight path in ascending order of their atomic mash; and
(c) employing a qating device comprising a first part and a send part, said first part having an aperture, wherein electrical potentials applied to said first part and said second part of said gating device selectively allow a portion of each of said pulses of ions to enter said mass analyzer from th end of said time of flight path and preventing the remainder of each of said pulses of ions from entering said mass analyzer.
1. Apparatus for delivering ions to a mass analyzer comprising:
(a) a time of flight ion guide having an entrance end and an exit end;
(b) a pulsing device for receiving a continuous ion stream containing ions of different atomic mass and for delivering pulses of ions from said continuous stream of ions into the entrance end of said ion guide so that ions in each of said pulses of ions reach the exit end of said ion guide in ascending order of their atomic mass; and
(c) a gating device at the exit end of said ion guide operating in timed sequence with said pulsing device for allowing only ions of a predetermined atomic mass in each of said pulses of ions to pass through said gating device to said mass analyzer,
wherein said gating device comprises a first part and a second part, said first part having an aperture, wherein electrical potentials applied to said first part and said second part of said gating device can selectively allow ions to pass through said aperture.
10. A mass spectrometer comprising:
(a) an ion source for producing a continuous ion stream containing ions of different atomic mass;
(b) a mass analyzer;
(c) a time of flight ion guide between said ion source and said mass analyzer, said time of flight ion guide having an entrance end and an exit end;
(d) a pulsing device between said ion source and said time of flight ion guide for receiving said continuous stream of ions and delivering pulses of ions from said stream of ions to the entrance end of said time of flight ion guide so that ions in each of said pulses of ions reach the exit end of said time of flight ion guide in ascending order of their atomic mass; and
(e) a gating device at the exit end of said ion guide operating in timed sequence with said pulsing device for allowing only ions of a predetermined atomic mass in each of said pulses of ions to pass through said gating device to said mass analyzer,
wherein said gating device comprises a first part and a second part, said first part having an aperture, wherein electrical potentials applied to said first part and said second part of said gating device can selectively allow ions to pass through said aperture.
2. The apparatus as recited in
3. The apparatus as recited in
4.The apparatus as recited in
5.The apparatus as recited in
(a) a first ion lens for receiving said continuous ion stream; and
(b) a second ion lens between said first ion lens and said ion guide for delivering said pulses of ions to said ion guide.
6. The apparatus as recited in
7. The apparatus as recited in
8. The apparatus as recited in
9.The apparatus as recited in
11. The mass spectrometer as recited in
12. The mass spectrometer as recited in
14. The mass spectrometer as recited in
(a) a first ion lens for receiving said continuous ion stream; and
(b) a second ion lens between said first ion lens and said ion guide for delivering said pulses of ions to said ion guide.
15. The mass spectrometer as recited in
16. The mass spectrometer as recited in
17. The mass spectrometer as recited in
18. The mass spectrometer as recited in
19. The mass spectrometer as recited in
21. The method as recited in
22. The method as recited in
23. The method as recited in
24. The method as recited in
26. A method as recited in claim 25, comprising blocking each of said pulses of ions at the end of said time of flight path at predetermined time intervals relative to the converting of said continuous ion stream into pulses of ions.
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NOT APPLICABLE
This invention has been created without the sponsorship or funding of any federally sponsored research or development program.
1. Field of the Invention
This invention relates to the field of mass spectrometry. More particularly, it relates to the field of tandem mass spectrometry.
2. Background of the Invention
In the field of tandem mass spectrometry, it is common to use different kinds of mass analyzers and mass filters in series to improve analytical performance of the combined system. However coupling between different mass analyzers is not always technically easy or even possible. The most common combinations of the mass analyzers are triple quadrupole instruments, where two linear quadrupole filters are connected by a collision cell positioned in-between. An efficient way to couple linear quadrupole, collision cell and a time of flight (TOF) analyzer is disclosed in EP1006559. Magnetic and electric sector analyzers are also commonly used in tandem. These instruments are typically expensive, free standing instruments. Several systems have been recently developed to couple an ion trap with a time of flight mass analyzer. For example, U.S. Pat. No. 5,569,917 describes a combination of an ion trap followed by time of flight mass analyzer. However, the resulting combination is characterized by substantially increased cost and the necessity to operate time of flight at very high energy to obtain reasonable accuracy and resolution of analysis readings.
In another tandem mass spectrometry system, the time of flight mass analyzer was coupled with a quadrupole collision cell followed by a second time of flight analyzer, see WO 0077823 and WO 0077822. In this configuration, it was possible to achieve fragmentation information for the molecule of interest using two time of flight mass analyzers. Like previous systems the final configuration is somewhat expensive and bulky.
In still another tandem mass spectrometry system, two linear quadrupoles were connected by a placing ion trap mass analyzer in-between (Kofel. P.; Peinhard, H.; Schlunegger, U.; Org. Mass Spectrum., 1991, 26, 463). This mass spectrometer system contained two precisionly machined quadrupoles. This results in a complex and expensive system with moderate performance, with the difficulty of coupling an ion beam from a quadrupole mass filter to an ion trap mass analyzer. These and other difficulties experienced with the prior art tandem mass spectrometry systems may be obviated by the present invention.
What is needed is an economical and efficient way to select ions of a specific mass range that can be injected into a mass analyzer from a continuous ion source to improve selectivity and sensitivity for the mass spectrometer system.
Apparatus for and method of delivering ions to a mass analyzer. The apparatus includes a time of flight ion guide, a pulsing device for receiving a continuous ion stream containing ions of different atomic mass and for delivering pulses of ions from the continuous stream of ions into the entrance end of the ion guide so that ions in each pulse reach the exit end of the ion guide in ascending order of their atomic mass, and a gating device at the exit end of the ion guide operating in timed sequence with the pulsing device for allowing only ions of a predetermined atomic mass in each pulse to pass through the gating device to the mass analyzer. The invention also includes a mass spectrometer that includes the apparatus for delivering ions described above.
The character of the invention, however, may be best understood by reference to one of its structural forms, as illustrated in the accompanying drawings, in which:
Referring to
The ion source 26 may be any ion source known in the art that can be used for generating ions from an analyte sample and delivering them to a mass spectrometer system. Examples include atmospheric pressure ionization (API) sources, such as electrospray (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) sources. The analyte sample may be in liquid or gas form, for example, and is introduced into the ion source 26 by means well known in the art. The ion source 26 communicates with an interface 9 that comprises functions of transmitting ions from the ion source 26 to the mass spectrometer system and, optionally, allowing a reduction of gas pressure from that of the ion source 26 to that of the mass spectrometer system. Interface 9 may be an orifice, a capillary, a tube, a passageway or any other such device for ion transport and, optionally, pressure reduction.
The exemplary mass spectrometer system comprises one or more vacuum chambers, for example chambers 15, 16 and 25 shown in
The various components of the mass spectrometer system shown in
The power supplies for each of the electrical components of the exemplary mass spectrometer system of the present invention are shown diagrammatically in FIG. 1. The power to interface 9 is indicated by block 54. The power supply to skimmer 14 and first ion guide 2 are represented by blocks 55 and 56, respectively. The power supply to lenses 10 and 20 are represented by block 57. The power supply to the split lens 27 is represented by block 58. Power supplies 57 and 58 are connected to a master clock represented by block 59 to insure that the lens 27 operates in timed sequence with the operation of the lenses 10 and 20. The power supply, i.e. radio frequency generator, to the second ion guide 4 is represented by block 60. The power supply to the quadrupole ion trap 28 is represented by block 61.
According to the present example of the invention, a continuous beam of ions 8 from the interface 9 pass through the skimmer 14 and enter the first or preliminary ion guide 2. The ions travel along a preliminary ion path through the ion guide 2 and accumulate in the ion pulse region 3. After accumulation, ions are pulsed out into the second ion guide 4, that serves as the free flight region for the time of flight mass separator 1. All of the pulsed ions have substantially the same energy. Therefore, the flight time of ions through the second ion guide 4 depends only on their m/z. The gating device 5 at the exit of the second ion guide operates with a controlled time delay, synchronized with the ion pulse and stays open also for a predetermined period of time. This allows only ions having masses within a selected m/z range to enter the ion trap mass analyzer 23.
A typical timing diagram for the control pulses is shown in FIG. 2. Ions are typically stored in the ion pulse region during D1 and P2 time intervals, then ions are pulsed out of region 3 during P1 time interval and the process continues in cycles. During the D1 time interval, the pulsed out ions separate in their positions along the longitudinal axis of the second ion guide 4 according their m/z values, while the new portion of ions is accumulated in the ion pulse region 3. The typical time for the pulses P1 is 10 microseconds, while the whole cycle (P1+D1+P2) is 100 microseconds, thus resulting in 10 kHz repetition rate.
In an example, the first ion guide 2 is an octapole ion guide 25 mm long with 3 mm inscribed diameter. The second ion guide 4 is 260 mm long with the same inscribed diameter as the first ion guide. Both ion guides 2 and 4 operated at 2.2 Mhz, 150 V peak-to-peak radio frequency voltage applied in the usual manner for an octapole RF ion guide. Pulsing device 11 comprises two lenses 10 and 20. Lens 20 has a 3.5 mm ID aperture 22. Lens 10 has an aperture 21 that is substantially larger than aperture 22. The pressure in the pulse region 3 is in the range of about 10 to about 10−1 mTorr, due to the neutral gas accompanying the ion beam 8 into first ion guide 2. The presence of the neutral gas is useful for the efficient ion accumulation in the pulse region 3. Several DC voltages are applied to the ion optical elements to produce continuous cycles of ion accumulation in the pulse region 3. Ion guide 2 is maintained typically at 1.8V DC, lens 10 at 1V DC, lens 20 is pulsed from 30V DC during ion accumulation to 0V DC during ion pulse out (P1), the second ion guide 4 is maintained at −21V.
The gating device 5 is a split lens, generally indicated by the reference numeral 27, shown also in FIG. 3. The split lens 27 is an electric lens comprising a first element 40 and a second element 50. The lens 27 has an aperture 41. A first portion 42 of the aperture 41 is located in the element 40. A second portion 52 of the aperture 41 is located in the element 50. Both lens elements 40 and 50 for the gating device 5 are maintained at the same potential of −5V during (P2) pulse to provide ion transmission for the ions of selected mass range. During the rest of the time, the lens element 50 is switched to −100V to deflect the ion beam. The ion lens 30 serves as a refocusing element to direct the ion beam into the ion trap 23 and is maintained at −70V for the experiments. Refocusing can be accomplished by any number of ion lenses known in the art for example, an aperture lens, a system of aperture lenses, one or more einzle lenses, a dc quadrapole lens system, a cylinder lens or system thereof, or any combination of the above lenses.
Tests with the system of the present invention were performed on a modified Ion Trap MSD instrument from Agilent Technologies, wherein the standard ion optics in the third vacuum chamber were replaced with TOF ion optics as described in the above described example. The standard calibration mix sample from Agilent Technologies (part# G2431A) was introduced through a standard electrospray nebulizer. This sample has several ion species across the complete range of the mass analyzer; with m/z of 118, 322, 622, 922, 1522, and 2122 Da.
Although examples of the invention are described, the invention is not limited to any particular implementation. For example, the radio frequency ion guide can be a quadrupole, hexapole or other multipole device, as well as a structure of rings or a multipole sliced into several segments as is well known in the art. The gating device can be of different geometry and design as well known in the prior art. The ion delivery system of the present invention can be used with different ionization techniques including electrospray, electron impact, etc. The ion delivery system of the present invention operates at relatively low energy and only allows ions within a predetermined mass range to enter the ion trap of quadrupole ion trap mass analyzer. This also may result in improved sensitivity, selectively and signal-to-noise ratio for the mass analyzer.
According to the present invention the time of flight mass separator can operate at unusually low accelerating energy (below several hundred volts), since ions are guided in free flight region by an ion guide (otherwise the ions would disperse). Low ion energy simplifies the design, and also results in small, portable instruments. Another advantage of the device may be high duty cycle (close to 100%), since ions can be accumulated in the ion pulse region for about the same period of time that it takes for the heavier mass of interest to reach the exit of the second ion guide. Also, since virtually no ions are lost during accumulation in the pulsed region, the ion transmission in the selected mass window may be close to 100%. Therefore, the tandem combination of a linear time of flight mass analyzer and an ion trap mass analyzer allows selecting a predetermined mass range to be injected into an ion trap without appreciable losses in the ion intensities. This results in filling the ion trap to capacity only with ions of interest within a specified mass range and rejecting the interfering matrix ions outside of the transmission window, thus improving sensitivity, selectivity and signal to noise ratio for the ion trap mass analyzer.
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